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A genetic linkage map of the laboratory rat, Rattus norvegicus

Abstract

We report the construction of the first complete genetic linkage map of the laboratory rat. By testing 1171 simple sequence length polymorphisms (SSLPs), we have identified 432 markers that show polymorphisms between the SHR and BN rat strains and mapped them in a single (SHR × BN) F2 intercross. The loci define 21 large linkage groups corresponding to the 21 rat chromosomes, together with a pair of nearby markers on chromosome 9 that are not linked to the rest of the map. Because 99.5% of the markers fall into one of the 21 large linkage groups, the maps appear to cover the vast majority of the rat genome. The availability of the map should facilitate whole genome scans for genes underlying qualitative and quantitative traits relevant to mammalian physiology and pathobiology.

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References

  1. 1

    Lindsey, J.R. Historical foundations in the laboratory rat. In The laboratory rat.(eds Baker, H.J., Lindsey, J. R. & Welsbroth, S. H.) 1–36 (Academic Press, New York, 1979).

  2. 2

    Greenhouse, D.D., Festing, M.F.W., Hasan, S. & Cohen, A.L. Inbred strains of rats in Genetic monitoring of inbred strains of rats (ed. Hedrich, H. J. ) (Gustav Fischer Vertag, Stuttgart, 1990).

  3. 3

    Robinson, R. Genetics of the Norway rat. (Pergamon Press, Oxford, 1965).

  4. 4

    Dietrich, W.F. et al. A genetic map of the mouse with 4,006 simple sequence length polymorphisms. Nature Genet. 7, 220–245 (1994).

  5. 5

    Copeland, N.G. et al. Genome maps IV: the mouse. Science 262, 67–82 (1993).

  6. 6

    Copeland, N.G. et al. A genetic linkage map of the mouse: current applications and future prospects. Science 262, 57–66 (1993).

  7. 7

    Yamada, J., Kuramoto, T. & Serikawa, T. A rat genetic linkage map and comparative maps for mouse or human homologous rat genes.Mamm. Genome 5, 63–83 (1994).

  8. 8

    Serikawa, T. et al. Rat gene mapping using PCR-analyzed microsatellites. Genetics 131, 701–721 (1992).

  9. 9

    Levan, G., Klinga, K., Szpirer, C. & Szpirer, J. Gene map of the rat (Rattus norvegicus). in Locus maps of complex genomes.5th edn, 1990 (eds O' Brien, S.J.) (Cold Spring Harbor Press, New York, 1989).

  10. 10

    Levan, G., Klinga-Levan, K., Szpirer, C. & Szpirer, J. Gene map of the rat (Rattus norvegicus) November 1992. in Locus maps of complex genomes. 6th edn (ed. O'Brien, S.J.) (Cold Spring Habor Press, New York, 1992).

  11. 11

    Dietrich, W. et al. A genetic map of the mouse suitable for typing intraspecific crosses. Genetics 131, 423–447 (1992).

  12. 12

    Szpirer, J., Levan, G., Thorn, M. & Szpirer, C. Gene mapping in the rat by mouse-rat somatic cell hybridization: synteny of the albumin and alpha-fetoprotein genes and assignment to chromosome 14. Cytogenet. Cell Genet. 38, 142–149 (1984).

  13. 13

    Kurtz, T.W., Simonet, L., Kren, V. & Pravenec, M. Gene mapping in experimental hypertension. in Genetic approaches for the control of coronary heart disease and hypertension.(eds. Berg, K., Bulyzhenkov, V., Corvol, P. & Christen, Y. ) 38–59 (Springer-Veriag, Heidelberg, 1991).

  14. 14

    Pravenec, M., Klir, P., Kren, V., Zicha, J. & Kunes, J. An analysis of spontaneous hypertension in spontaneously hypertensive rats by means of new recombinant inbred strains. J. Hypertension 7, 217–221 (1989).

  15. 15

    Donis-Keller, H. et al. A genetic linkage map of the human genome. Cell 51, 319–337 (1987).

  16. 16

    Hofker, M.H. et al. The X chromosome shows less genetic variation at restriction sites than the autosomes. Am J. hum. Genet. 3, 438–451 (1986).

  17. 17

    Crow, J.F. How much do we know about spontaneous human mutation rates?(published erratum appears in 21:389. ). Environ molec. Mutagen. 21, 122–129 (1993).

  18. 18

    Buard, J. & Vergnaud, G. Complex recombination events at the hypermutable minisatellite CEB 1 (D2S90). EMBO J. 13, 3203–3210 (1994).

  19. 19

    Weber, J.L. & Wong, C. Mutation of human short tandem repeats. Hum. molec. Genet. 2, 1123–1128 (1993).

  20. 20

    Church, G.M. & Gilbert, W. Genomic sequencing. Proc. natn. Acad. Sci. U.S.A. 81, 1991–1995 (1984).

  21. 21

    Sambrook, J., Fritsch, E.F. & Manltatls, T. Molecular cloning: A laboratory manual. (Cold Spring Harbor Laboratory Press, New York, 1989).

  22. 22

    Jacob, H.J. et al. Genetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat. Cell 67, 213–224 (1991).

  23. 23

    Lander, E.S. et al. MAPMAKER — an interactive computer package for constructing primary genetic linkage maps of experimental and natural populations. Genomics 1, 174 (1987).

  24. 24

    Lincoln, S.E. & Lander, E.S. Systematic detection of errors in genomic linkage data. Genomics 14, 604–610 (1992).

  25. 25

    Definition, Nomenclature, and conservation of rat strains. ILAR News 34, S1–S26 (1993).

  26. 26

    Tay, A., Simon, J.S., Squire, J., Jacob, H.J. & Skorecki, K., Cytosolic phosphollpase A2 gene in human and rat: Chromosomal localization and polymorphic markers. Genomics(in the press).

  27. 27

    Levin, M.S., Li, E., Ong, D.E. & Gordon, J.I. Comparison of the tissue-specific expression and developmental regulation of two closely linked rodent genes encoding cytosolic retinol binding proteins. J. biol. Chem. 262, 7118–7124 (1987).

  28. 28

    Matsuyama, M. et al. Genetic regulation of the development of glomerular sclerotic lesions in the BUF/Mna rat. Nephron 54, 334–37 (1990).

  29. 29

    Cox, J.L. & Shaw, P.A. Structure, organization and regulation of a rat cysteine proteinase inhibitor-encoding gene. Gene 110, 175–180 (1992).

  30. 30

    Ozer, J., Chalkey, R. & L, S. Characterization of rat pseudogenes for enhancer factor I subunit A: ripping provides clues to the evolution of the EFIA/dbp B/YB-1 multigene family. Gene 133, 187–195 (1993).

  31. 31

    Das, A.T. et al. Isolation and characterization of the rat gene encoding glutamate dehydrogenase. Eur. J. Biochem. 211, 795–803 (1993).

  32. 32

    Pettersson, S., Cook, G.P., Bruggemann, M., Williams, G.T. & Neuberger, M.S. A second B cell-specific enhancer 3″ of the immunoglobulin heavy-chain locus.Nature 344, 165–168 (1990).

  33. 33

    Richter, G., Blankenstein, T. & Diamantstein, T. Evolutionary aspects, structure and expression of the rat interieukin 4 gene. Cytokine 2, 221–228 (1990).

  34. 34

    Ching, G. & Liem, R. Structure of the gene for neuronal intermediate filament protein alpha-internexin and functional analysis of its promoter. J. biol. Chem. 266, 19459–19468 (1991).

  35. 35

    Shier, P. & Watt, V.M. Tissue-specific expression of the rat insulin receptor-related receptor gene. Molec. Endocrin. 6, 723–729 (1992).

  36. 36

    D'Ambrosio, E., Waitzkin, S.D., Witney, F.R., Salemme, A. & Furano, A.V. Structure of the highly repeated, long interspersed DNA family LINE or L1 Rn of the rat. Molec. Cell Biol. 6, 411–424 (1986).

  37. 37

    Dancinger, E., Mettling, C., Vidal, M., Morris, R. & Margolis, F. Olfactory marker protein gene: its structure and olfactory neuron-specific expression in transgenic mice. Proc. natn. Acad. Sci. U.S.A. 86, 8565–8569 (1989).

  38. 38

    Gil-Gomez, G., Ayte, J. & Hegardt, F.G. The rat mitochondrial 3-Hydroxy-3-methylglutaryl-coenzyme-A-synthase gene contains elements that mediate its multihormonal reguations and tissue specificity. Eur. J. Biochem. 213, 773–779 (1993).

  39. 39

    Deuchars, K.L., Duthie, M. & Ling, V. Identification of distinct P-glycoprotein gene sequences in rat. Biochim. Biophys. Acta 1130, 157–165 (1992).

  40. 40

    Sprengel, R. et al. Molecular cloning and expression of cDNA encoding a peripheral-type benzodiazepine receptor. J. biol. Chem. 264, 20415–20421 (1989).

  41. 41

    Bargou, R.C.E.F. & Leube, R.E., Synaptophysin-encoding gene in rat and man is specifically transcribed in neuroendocrine cells. Gene 99, 197–204 (1991).

  42. 42

    Lees-Miller, P.A. & Helfman, D.M. Structure and complete nucleoride sequence of the gene encoding rat fibroblast tropomyosin 4. J. molec. Biol. 213, 399–405 (1990).

  43. 43

    Holloway, M.P. & LaGamma, E.F. Tissue specific control of the tranascription of the rat proenkephalin gene. Thesis (Dept. Pediatrics, SUNY at Stony Brook (1993).

  44. 44

    Watanabe, N. & Ohshima, Y. Three types of rat U1 small nuclear RNA genes with different flanking sequences are induced to express in vivo. Eur. J. Biochem. 174, 125–132 (1988).

  45. 45

    Motojima, K. & Goto, S. Organization of rat uricase chromosomal gene differs greatly from that of the corresponding plant gene. FEBS Lett. 264, 156–158 (1990).

  46. 46

    Kuramoto, K., Malhara, T., Masu, M., Nakanishi, S. & Serikawa, T. Gene mapping of NMDA receptors and metabotropic glutamate receptors in the rat (Rattus norvegicus ). Genomics. 19, 351–361 (1994).

  47. 47

    Goldmuntz, E. et al. Genetic map of 12 polymorphic loci on rat chromosome 1. Genomics. 16, 761–764 (1993).

  48. 48

    Zha, H. et al. Linkage map of 10 polymorphic markers on rat chromosome 2.Cytogenet. Cell Genet. 63, 117–123 (1994).

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